Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2

doi:10.1016/j.bioorg.2018.01.011

	Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2
	Zou, Li-Wei 3; Weng, Zi-Miao 2; Ge, Guang-Bo 3,4; Dou, Tong-Yi 1,4; Wang, Ping 3; Liu, Ping-Kun 2; Tian, Xin-Hui 3; Qiao, Nan 1; Yu, Yang 3; Zhou, Qi 2
刊名	BIOORGANIC CHEMISTRY
	2018-04-01
卷号	77 页码:320-329
关键词	Flavonoids Human Carboxylesterase 2 (Hce2) Structure-inhibition Relationships Selectivity Inhibition Mechanism
ISSN号	0045-2068
DOI	10.1016/j.bioorg.2018.01.011
文献子类	Article
英文摘要	Human carboxylesterases (hCEs) are key enzymes from the serine hydrolase superfamily. Among all identified hCEs, human carboxylesterase 2 (hCE2) plays crucial roles in the metabolic activation of ester drugs including irinotecan and flutamide. Selective and potent hCE2 inhibitors could be used to alleviate the toxicity induced by hCE2-substrate drugs. In this study, more than fifty flavonoids were collected to assay their inhibitory effects against hCE2 using a fluorescence-based method. The results demonstrated that C3 and C6 hydroxy groups were essential for hCE2 inhibition, while O-glycosylation or C-glycosylation would lead to the loss of hCE2 inhibition. Among all tested flavonoids, 5,6-dihydroxyflavone displayed the most potent inhibitory effect against hCE2 with the IC50 value of 3.50 mu M. The inhibition mechanism of 5,6-dihydroxyflavone was further investigated by both experimental and docking simulations. All these findings are very helpful for the medicinal chemists to design and develop more potent and highly selective flavonoid-type hCE2 inhibitors. (C) 2018 Published by Elsevier Inc.
WOS关键词	SELECTIVE INHIBITORS ; INTESTINAL CARBOXYLESTERASE ; CATALYTIC-PROPERTIES ; NATURAL INHIBITORS ; INDUCED DIARRHEA ; HUMAN LIVER ; IRINOTECAN ; ISOZYMES ; TRITERPENOIDS ; ACTIVATION
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000428013300034
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/169108]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Hou, Jie
作者单位	1.Dalian Univ Technol, Sch Life Sci & Med, Panjin 124221, Peoples R China 2.Dalian Med Univ, Dalian 116044, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Med, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
推荐引用方式 GB/T 7714	Zou, Li-Wei,Weng, Zi-Miao,Ge, Guang-Bo,et al. Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2[J]. BIOORGANIC CHEMISTRY,2018,77:320-329.
APA	Zou, Li-Wei.,Weng, Zi-Miao.,Ge, Guang-Bo.,Dou, Tong-Yi.,Wang, Ping.,...&Hou, Jie.(2018).Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2.BIOORGANIC CHEMISTRY,77,320-329.
MLA	Zou, Li-Wei,et al."Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2".BIOORGANIC CHEMISTRY 77(2018):320-329.